Mechanophysical Stimulations of Mucin Secretion in Cultures of Nasal Epithelial Cells

Davidovich, Nurit; Kloog, Yoel; Wolf, Michael; Elad, David

doi:10.1016/j.bpj.2011.04.040

Cited by 21 publications

(6 citation statements)

References 61 publications

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“…A similar outcome of denser and more stabilized microtubules in the cell cytoplasm and around the cell nucleus was also observed in endothelial cells exposed to steady WSS of 15–20 dyne/cm 2 for 24 hours exhibited [22], [36], [37]. It is noteworthy that steady WSS applied on nasal epithelial cells induced microtubules fragmentation, while oscillatory WSS resulted in a more organized and filamentous microtubules network in the cytoplasm, including the generation of new microtubules [17], [25]. In another study, metastatic esophageal cancer cells that were exposed to venous shear rate of 200 for 30 minutes showed rapid polymerization and trans-location of tubulin to the leading edge of the cell opposed to cortical ring localization under static conditions [12].…”

Section: Discussionsupporting

confidence: 56%

“…It should be noted that elongation of the cells was reported to occur after much shorter exposure time to shear stress [13], [23]. The abovementioned shape change response of endothelial cells to WSS (i.e., elongation and orientation in the flow direction) was assumed cell-specific, since it was not observed in smooth muscle cells and nasal epithelial cells [25], [26], [27]. The present outcome may also be related to the elasticity of the amniotic mambrene on which the EOC cells were cultured.…”

Section: Discussionmentioning

confidence: 99%

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Fluid-Flow Induced Wall Shear Stress and Epithelial Ovarian Cancer Peritoneal Spreading

et al. 2013

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Epithelial ovarian cancer (EOC) is usually discovered after extensive metastasis have developed in the peritoneal cavity. The ovarian surface is exposed to peritoneal fluid pressures and shear forces due to the continuous peristaltic motions of the gastro-intestinal system, creating a mechanical micro-environment for the cells. An in vitro experimental model was developed to expose EOC cells to steady fluid flow induced wall shear stresses (WSS). The EOC cells were cultured from OVCAR-3 cell line on denuded amniotic membranes in special wells. Wall shear stresses of 0.5, 1.0 and 1.5 dyne/cm2 were applied on the surface of the cells under conditions that mimic the physiological environment, followed by fluorescent stains of actin and β-tubulin fibers. The cytoskeleton response to WSS included cell elongation, stress fibers formation and generation of microtubules. More cytoskeletal components were produced by the cells and arranged in a denser and more organized structure within the cytoplasm. This suggests that WSS may have a significant role in the mechanical regulation of EOC peritoneal spreading.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Fluid-Flow Induced Wall Shear Stress and Epithelial Ovarian Cancer Peritoneal Spreading

et al. 2013

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“…With additional cultivation on the chip, the cell density decreased slightly in each case, but cilia formation could be still promoted. These results are in accordance with the literature, where the increase in mucin secretion was around 30-80%, as obtained with primary human nasal epithelial cells, after a WSS of 0.05 Pa and 0.5 Pa respectively, for a time period of 5 min, as was previously described in [45]. Furthermore, the influence of mechanophysical stimulation on mucus secretion was reported to be affected more strongly by the time length of WSS than by the level of WSS [46].…”

Section: Formation Of Ciliasupporting

confidence: 93%

“…described in [45]. Furthermore, the influence of mechanophysical stimulation on mucus secretion was reported to be affected more strongly by the time length of WSS than by the level of WSS [46].…”

Section: Mucus Productionmentioning

confidence: 99%

The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing

Koch,

Bendas,

Nehlsen

et al. 2023

Pharmaceutics

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The nasal mucosa, being accessible and highly vascularized, opens up new opportunities for the systemic administration of drugs. However, there are several protective functions like the mucociliary clearance, a physiological barrier which represents is a difficult obstacle for drug candidates to overcome. For this reason, effective testing procedures are required in the preclinical phase of pharmaceutical development. Based on a recently reported immortalized porcine nasal epithelial cell line, we developed a test platform based on a tissue-compatible microfluidic chip. In this study, a biomimetic glass chip, which was equipped with a controlled bidirectional airflow to induce a physiologically relevant wall shear stress on the epithelial cell layer, was microfabricated. By developing a membrane transfer technique, the epithelial cell layer could be pre-cultivated in a static holder prior to cultivation in a microfluidic environment. The dynamic cultivation within the chip showed a homogenous distribution of the mucus film on top of the cell layer and a significant increase in cilia formation compared to the static cultivation condition. In addition, the recording of the ciliary transport mechanism by microparticle image velocimetry was successful. Using FITC-dextran 4000 as an example, it was shown that this nasal mucosa on a chip is suitable for permeation studies. The obtained permeation coefficient was in the range of values determined by means of other established in vitro and in vivo models. This novel nasal mucosa on chip could, in future, be automated and used as a substitute for animal testing.

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“…An enhanced permeation performance of aerosolized NPs was observed when a 15 L/min airflow was applied (Figure ). The respiratory airflow, in both static and oscillatory patterns, exposes the nasal epithelium to wall shear stresses which have been shown to cause significant yet temporary structural and functional alterations of the ALI-human nasal epithelium. , It was reported that the main response to such stresses is an increase in epithelial cell mucus secretion (mucins and water) and, hence, a decrease in the transport rate across the mucosa and a simultaneous increase in NP accumulation on/within the cell layer may be expected. This impact, however, was subject to the duration of the stress stimulus, which was >15 min, rather than the magnitude of the wall shear stress .…”

Section: Discussionmentioning

confidence: 99%

A Cell-Based Nasal Model for Screening the Deposition, Biocompatibility, and Transport of Aerosolized PLGA Nanoparticles

Maaz,

Blagbrough,

De Bank

2024

Mol. Pharmaceutics

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The olfactory region of the nasal cavity directly links the brain to the external environment, presenting a potential direct route to the central nervous system (CNS). However, targeting drugs to the olfactory region is challenging and relies on a combination of drug formulation, delivery device, and administration technique to navigate human nasal anatomy. In addition, in vitro and in vivo models utilized to evaluate the performance of nasal formulations do not accurately reflect deposition and uptake in the human nasal cavity. The current study describes the development of a respirable poly(lactic-co-glycolic acid) nanoparticle (PLGA NP) formulation, delivered via a pressurized metered dose inhaler (pMDI), and a cell-containing three-dimensional (3D) human nasal cast model for deposition assessment of nasal formulations in the olfactory region. Fluorescent PLGA NPs (193 ± 3 nm by dynamic light scattering) were successfully formulated in an HFA134a-based pMDI and were collected intact following aerosolization. RPMI 2650 cells, widely employed as a nasal epithelial model, were grown at the air–liquid interface (ALI) for 14 days to develop a suitable barrier function prior to exposure to the aerosolized PLGA NPs in a glass deposition apparatus. Direct aerosol exposure was shown to have little effect on cell viability. Compared to an aqueous NP suspension, the transport rate of the aerosolized NPs across the RPMI 2650 barrier was higher at all time points indicating the potential advantages of delivery via aerosolization and the importance of employing ALI cellular models for testing respirable formulations. The PLGA NPs were then aerosolized into a 3D-printed human nasal cavity model with an insert of ALI RPMI 2650 cells positioned in the olfactory region. Cells remained highly viable, and there was significant deposition of the fluorescent NPs on the ALI cultures. This study is a proof of concept that pMDI delivery of NPs is a viable means of targeting the olfactory region for nose-to-brain drug delivery (NTBDD). The cell-based model allows not only maintenance under ALI culture conditions but also sampling from the basal chamber compartment; hence, this model could be adapted to assess drug deposition, uptake, and transport kinetics in parallel under real-life settings.

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Mechanophysical Stimulations of Mucin Secretion in Cultures of Nasal Epithelial Cells

Cited by 21 publications

References 61 publications

Fluid-Flow Induced Wall Shear Stress and Epithelial Ovarian Cancer Peritoneal Spreading

Fluid-Flow Induced Wall Shear Stress and Epithelial Ovarian Cancer Peritoneal Spreading

The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing

A Cell-Based Nasal Model for Screening the Deposition, Biocompatibility, and Transport of Aerosolized PLGA Nanoparticles

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